PE20081346A1 - Derivados de espiroindolinona como antagonistas de mdm2 - Google Patents
Derivados de espiroindolinona como antagonistas de mdm2Info
- Publication number
- PE20081346A1 PE20081346A1 PE2007001533A PE2007001533A PE20081346A1 PE 20081346 A1 PE20081346 A1 PE 20081346A1 PE 2007001533 A PE2007001533 A PE 2007001533A PE 2007001533 A PE2007001533 A PE 2007001533A PE 20081346 A1 PE20081346 A1 PE 20081346A1
- Authority
- PE
- Peru
- Prior art keywords
- diona
- rac
- indol
- chlorophenyl
- cyclohexane
- Prior art date
Links
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 title abstract 2
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 title abstract 2
- 239000005557 antagonist Substances 0.000 title abstract 2
- -1 CYANE Chemical class 0.000 abstract 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract 3
- 150000001875 compounds Chemical class 0.000 abstract 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- XIPUIGPNIDKXJU-UHFFFAOYSA-N [CH]1CC1 Chemical class [CH]1CC1 XIPUIGPNIDKXJU-UHFFFAOYSA-N 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 230000004663 cell proliferation Effects 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 230000003993 interaction Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/54—Spiro-condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
REFERIDA A UN COMPUESTO DERIVADO DE ESPIROINDOLINONA DE FORMULA (Ia) O (Ib), DONDE X ES H, HALOGENO, CIANO, NITRO, ETINILO O CICLOPROPILO; Y ES HIDROGENO; R1, R2, R3 Y R4 SON H, ALQUILO, HETEROCICLO, CICLOALQUILO, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: RAC-(1R,2S,6S)-6'-CLORO-2-(3-CLOROFENIL)-6-METOXIESPIRO[CICLOHEXANO-1,3'-[3H]INDOL]-2',4(1'H)-DIONA, RAC-(1S,2S,6R)-6'-CLORO-2-(3-CLOROFENIL)-6-(5-FLUOR-2-METIL-FENIL)ESPIRO[CICLOHEXANO-1,3'-[3H]INDOL]-2',4(1'H)-DIONA, RAC-(1R,2S,6S)-6'-CLORO-2-(3-CLOROFENIL)-6-CICLOPROPILESPIRO-[CICLOHEXANO-1,3'-[3H]INDOL]-2',4(1'H)-DIONA, ENTRE OTROS. TAMBIEN ESTA REFERIDA A UNA FORMULACION FARMACEUTICA. DICHOS COMPUESTOS TIENEN ACTIVIDAD ANTAGONISTA EN LAS INTERACCIONES DE LA PROTEINA MDM2 Y SON UTILES EN EL TRATAMIENTO O CONTROL DE TRASTORNOS DE PROLIFERACION CELULAR COMO EL CANCER
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US85803906P | 2006-11-09 | 2006-11-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
PE20081346A1 true PE20081346A1 (es) | 2008-10-24 |
Family
ID=38942414
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PE2007001533A PE20081346A1 (es) | 2006-11-09 | 2007-11-07 | Derivados de espiroindolinona como antagonistas de mdm2 |
Country Status (16)
Country | Link |
---|---|
US (1) | US7638548B2 (es) |
EP (1) | EP2089360B1 (es) |
JP (1) | JP2010509260A (es) |
KR (1) | KR20090095563A (es) |
CN (1) | CN101535255A (es) |
AR (1) | AR063602A1 (es) |
AT (1) | ATE512135T1 (es) |
AU (1) | AU2007316740A1 (es) |
CA (1) | CA2668398A1 (es) |
CL (1) | CL2007003202A1 (es) |
ES (1) | ES2364784T3 (es) |
IL (1) | IL198319A0 (es) |
MX (1) | MX2009004766A (es) |
PE (1) | PE20081346A1 (es) |
TW (1) | TW200829551A (es) |
WO (1) | WO2008055812A1 (es) |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8134001B2 (en) * | 2007-12-14 | 2012-03-13 | Hoffmann-La Roche Inc. | Spiroindolinone derivatives |
US7776875B2 (en) * | 2007-12-19 | 2010-08-17 | Hoffman-La Roche Inc. | Spiroindolinone derivatives |
US7723372B2 (en) * | 2008-03-19 | 2010-05-25 | Hoffman-La Roche Inc. | Spiroindolinone derivatives |
US20110269812A1 (en) * | 2008-10-14 | 2011-11-03 | Agency For Science, Technology And Research | Novel benzylidene-indolinone and their medical and diagnostic uses |
US20100190814A1 (en) * | 2009-01-26 | 2010-07-29 | Li Chen | Spiroindolinone derivative prodrugs |
US7928233B2 (en) * | 2009-02-10 | 2011-04-19 | Hoffmann-La Roche Inc. | Spiroindolinone pyridine derivatives |
US8217051B2 (en) * | 2009-02-17 | 2012-07-10 | Hoffmann-La Roche Inc. | Spiroindolinone derivatives |
US8076482B2 (en) | 2009-04-23 | 2011-12-13 | Hoffmann-La Roche Inc. | 3,3′-spiroindolinone derivatives |
CN104876938A (zh) * | 2009-11-12 | 2015-09-02 | 密歇根大学董事会 | 螺-吲哚酮mdm2拮抗剂 |
US8088815B2 (en) * | 2009-12-02 | 2012-01-03 | Hoffman-La Roche Inc. | Spiroindolinone pyrrolidines |
US8288431B2 (en) * | 2010-02-17 | 2012-10-16 | Hoffmann-La Roche Inc. | Substituted spiroindolinones |
US8217044B2 (en) | 2010-04-28 | 2012-07-10 | Hoffmann-La Roche Inc. | Spiroindolinone pyrrolidines |
JP2014500870A (ja) | 2010-11-12 | 2014-01-16 | ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、ミシガン | スピロ−オキシインドールmdm2アンタゴニスト |
MX342958B (es) | 2011-03-10 | 2016-10-18 | Daiichi Sankyo Co Ltd | Derivados de diespiropirrolidina. |
CN102180828A (zh) * | 2011-03-31 | 2011-09-14 | 四川大学 | 手性吲哚啉酮螺五环骨架化合物及不对称合成 |
EP2707372B1 (en) | 2011-05-11 | 2016-12-21 | The Regents Of The University Of Michigan | Spiro-oxindole mdm2 antagonists |
TWI586668B (zh) | 2012-09-06 | 2017-06-11 | 第一三共股份有限公司 | 二螺吡咯啶衍生物之結晶 |
ES2707305T3 (es) | 2012-12-20 | 2019-04-03 | Merck Sharp & Dohme | Imidazopiridinas sustituidas como inhibidores de HDM2 |
CN103992334A (zh) * | 2014-05-29 | 2014-08-20 | 中国人民解放军第二军医大学 | 吲哚酮螺四氢硫代吡喃类抗肿瘤衍生物及其制备方法 |
JP6564449B2 (ja) | 2015-02-20 | 2019-08-21 | 第一三共株式会社 | がんの併用治療法 |
CN107530336B (zh) | 2015-04-13 | 2020-09-25 | 第一三共株式会社 | 组合使用mdm2抑制剂和btk抑制剂的治疗方法 |
AU2017246452C1 (en) | 2016-04-06 | 2021-06-03 | The Regents Of The University Of Michigan | MDM2 protein degraders |
EP3440082A1 (en) | 2016-04-06 | 2019-02-13 | The Regents of The University of Michigan | Monofunctional intermediates for ligand-dependent target protein degradation |
JP2019522633A (ja) | 2016-05-20 | 2019-08-15 | ジェネンテック, インコーポレイテッド | Protac抗体コンジュゲート及び使用方法 |
KR20190068544A (ko) | 2016-10-17 | 2019-06-18 | 다이이찌 산쿄 가부시키가이샤 | Mdm2 저해제와 dna 메틸트랜스페라아제 저해제의 병용 치료법 |
US11046703B2 (en) | 2018-10-08 | 2021-06-29 | The Regents Of The University Of Michigan | Small molecule MDM2 protein degraders |
EP4121043A4 (en) | 2020-03-19 | 2024-07-24 | Kymera Therapeutics, Inc. | Mdm2 degraders and uses thereof |
CN113149890B (zh) * | 2021-04-27 | 2023-01-03 | 华东理工大学 | 合成3-螺-2-吲哚酮类化合物的方法 |
WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
CN116354786A (zh) * | 2021-12-27 | 2023-06-30 | 北京化工大学 | 一种碗状并苯类化合物,制备及应用 |
WO2024240858A1 (en) | 2023-05-23 | 2024-11-28 | Valerio Therapeutics | Protac molecules directed against dna damage repair system and uses thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0947511A1 (en) | 1998-03-30 | 1999-10-06 | F. Hoffmann-La Roche Ag | Derivatives of phenoxy acetic acid and of phenoxymethyl tetrazole having antitumor activity |
HUP9902374A3 (en) * | 1999-07-15 | 2002-11-28 | Sanofi Aventis | Process for producing spiro[(4-cyclohexanone)-[3h]indol-2'[1'h]-on derivatives and intermediates |
EA014445B1 (ru) * | 2005-02-22 | 2010-12-30 | Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган | Низкомолекулярные ингибиторы mdm2 и их применения |
US7553833B2 (en) * | 2007-05-17 | 2009-06-30 | Hoffmann-La Roche Inc. | 3,3-spiroindolinone derivatives |
-
2007
- 2007-10-04 US US11/867,155 patent/US7638548B2/en not_active Expired - Fee Related
- 2007-10-30 CA CA002668398A patent/CA2668398A1/en not_active Abandoned
- 2007-10-30 CN CNA2007800416354A patent/CN101535255A/zh active Pending
- 2007-10-30 EP EP07822025A patent/EP2089360B1/en not_active Not-in-force
- 2007-10-30 KR KR1020097009486A patent/KR20090095563A/ko not_active Ceased
- 2007-10-30 JP JP2009535672A patent/JP2010509260A/ja active Pending
- 2007-10-30 AT AT07822025T patent/ATE512135T1/de not_active IP Right Cessation
- 2007-10-30 AU AU2007316740A patent/AU2007316740A1/en not_active Abandoned
- 2007-10-30 MX MX2009004766A patent/MX2009004766A/es active IP Right Grant
- 2007-10-30 ES ES07822025T patent/ES2364784T3/es active Active
- 2007-10-30 WO PCT/EP2007/061671 patent/WO2008055812A1/en active Application Filing
- 2007-11-06 CL CL200703202A patent/CL2007003202A1/es unknown
- 2007-11-07 PE PE2007001533A patent/PE20081346A1/es not_active Application Discontinuation
- 2007-11-07 AR ARP070104959A patent/AR063602A1/es unknown
- 2007-11-07 TW TW096142122A patent/TW200829551A/zh unknown
-
2009
- 2009-04-23 IL IL198319A patent/IL198319A0/en unknown
Also Published As
Publication number | Publication date |
---|---|
AU2007316740A1 (en) | 2008-05-15 |
AR063602A1 (es) | 2009-02-04 |
EP2089360B1 (en) | 2011-06-08 |
JP2010509260A (ja) | 2010-03-25 |
US7638548B2 (en) | 2009-12-29 |
KR20090095563A (ko) | 2009-09-09 |
IL198319A0 (en) | 2010-02-17 |
TW200829551A (en) | 2008-07-16 |
MX2009004766A (es) | 2009-05-21 |
CN101535255A (zh) | 2009-09-16 |
CL2007003202A1 (es) | 2008-03-07 |
EP2089360A1 (en) | 2009-08-19 |
ATE512135T1 (de) | 2011-06-15 |
WO2008055812A1 (en) | 2008-05-15 |
ES2364784T3 (es) | 2011-09-14 |
US20080114013A1 (en) | 2008-05-15 |
CA2668398A1 (en) | 2008-05-15 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
FA | Abandonment or withdrawal |